diff --git a/Lib/test/support/__init__.py b/Lib/test/support/__init__.py
index ca903d302bdd31..91cfca9f4b6226 100644
--- a/Lib/test/support/__init__.py
+++ b/Lib/test/support/__init__.py
@@ -56,6 +56,7 @@
     "run_with_tz", "PGO", "missing_compiler_executable",
     "ALWAYS_EQ", "NEVER_EQ", "LARGEST", "SMALLEST",
     "LOOPBACK_TIMEOUT", "INTERNET_TIMEOUT", "SHORT_TIMEOUT", "LONG_TIMEOUT",
+    "repeat_cpython_adaptative",
     ]
 
 
@@ -2118,3 +2119,27 @@ def clear_ignored_deprecations(*tokens: object) -> None:
     if warnings.filters != new_filters:
         warnings.filters[:] = new_filters
         warnings._filters_mutated()
+
+
+def repeat_cpython_adaptative(f):
+    """Runs a test multiple times. First with PEP 659 adaptive opcodes, then
+    with specialized opcodes once the opcodes turn "hot". This catches bugs
+    related to specialized opcodes.
+
+    See bpo-46465 for an example bug affecting only specialized opcodes,
+    due to a missing CHECK_EVAL_BREAKER.
+    """
+    # _co_warmedup is only available in CPython
+    if check_impl_detail(cpython=True) and hasattr(f.__code__, "_co_warmedup"):
+        @functools.wraps(f)
+        def wrapper(self):
+            done = False
+            while not done:
+                is_warmedup = f.__code__._co_warmedup
+                if is_warmedup:
+                    done = True
+                with self.subTest(cpython_is_warmedup=is_warmedup):
+                    f(self)
+        return wrapper
+    else:
+        return f
diff --git a/Lib/unittest/test/test_break.py b/Lib/unittest/test/test_break.py
index eebd2b610ce11f..195466a2ec9a47 100644
--- a/Lib/unittest/test/test_break.py
+++ b/Lib/unittest/test/test_break.py
@@ -6,6 +6,7 @@
 import weakref
 
 import unittest
+from test.support import repeat_cpython_adaptative
 
 
 @unittest.skipUnless(hasattr(os, 'kill'), "Test requires os.kill")
@@ -23,7 +24,9 @@ def tearDown(self):
         unittest.signals._results = weakref.WeakKeyDictionary()
         unittest.signals._interrupt_handler = None
 
-
+    # Tests both adaptive and specialized opcodes for proper
+    # CHECK_EVAL_BREAKER(). See bpo-46465 for an example bug.
+    @repeat_cpython_adaptative
     def testInstallHandler(self):
         default_handler = signal.getsignal(signal.SIGINT)
         unittest.installHandler()
@@ -121,7 +124,9 @@ def test(result):
         self.assertTrue(result2.shouldStop)
         self.assertFalse(result3.shouldStop)
 
-
+    # Tests both adaptive and specialized opcodes for proper
+    # CHECK_EVAL_BREAKER(). See bpo-46465 for an example bug.
+    @repeat_cpython_adaptative
     def testHandlerReplacedButCalled(self):
         # Can't use skipIf decorator because the signal handler may have
         # been changed after defining this method.
diff --git a/Misc/NEWS.d/next/Core and Builtins/2022-01-23-21-01-28.bpo-46465.z25Vbj.rst b/Misc/NEWS.d/next/Core and Builtins/2022-01-23-21-01-28.bpo-46465.z25Vbj.rst
new file mode 100644
index 00000000000000..d0313cb78351f8
--- /dev/null
+++ b/Misc/NEWS.d/next/Core and Builtins/2022-01-23-21-01-28.bpo-46465.z25Vbj.rst	
@@ -0,0 +1,2 @@
+Properly check for eval loop breaker in specialized ``CALL`` opcodes. Patch
+by Victor Stinner and Ken Jin.
diff --git a/Objects/codeobject.c b/Objects/codeobject.c
index a413b183be8edc..863ddd908a9d77 100644
--- a/Objects/codeobject.c
+++ b/Objects/codeobject.c
@@ -1542,6 +1542,17 @@ code_getfreevars(PyCodeObject *code, void *closure)
     return _PyCode_GetFreevars(code);
 }
 
+static PyObject *
+code_iswarmedup(PyCodeObject *code, void *closure)
+{
+    if (code->co_quickened != NULL) {
+        Py_RETURN_TRUE;
+    }
+    else {
+        Py_RETURN_FALSE;
+    }
+}
+
 static PyGetSetDef code_getsetlist[] = {
     {"co_lnotab",    (getter)code_getlnotab, NULL, NULL},
     // The following old names are kept for backward compatibility.
@@ -1549,6 +1560,7 @@ static PyGetSetDef code_getsetlist[] = {
     {"co_varnames",  (getter)code_getvarnames, NULL, NULL},
     {"co_cellvars",  (getter)code_getcellvars, NULL, NULL},
     {"co_freevars",  (getter)code_getfreevars, NULL, NULL},
+    {"_co_warmedup", (getter)code_iswarmedup, NULL, NULL},
     {0}
 };
 
diff --git a/Python/ceval.c b/Python/ceval.c
index 9aaddd99edacf7..6299212ae79406 100644
--- a/Python/ceval.c
+++ b/Python/ceval.c
@@ -4752,6 +4752,7 @@ _PyEval_EvalFrameDefault(PyThreadState *tstate, InterpreterFrame *frame, int thr
             if (res == NULL) {
                 goto error;
             }
+            CHECK_EVAL_BREAKER();
             DISPATCH();
         }
 
@@ -4783,6 +4784,7 @@ _PyEval_EvalFrameDefault(PyThreadState *tstate, InterpreterFrame *frame, int thr
             if (res == NULL) {
                 goto error;
             }
+            CHECK_EVAL_BREAKER();
             DISPATCH();
         }
 
@@ -4822,6 +4824,7 @@ _PyEval_EvalFrameDefault(PyThreadState *tstate, InterpreterFrame *frame, int thr
                 */
                 goto error;
             }
+            CHECK_EVAL_BREAKER();
             DISPATCH();
         }
 
@@ -4881,6 +4884,7 @@ _PyEval_EvalFrameDefault(PyThreadState *tstate, InterpreterFrame *frame, int thr
             if (res == NULL) {
                 goto error;
             }
+            CHECK_EVAL_BREAKER();
             DISPATCH();
         }
 
@@ -4939,6 +4943,7 @@ _PyEval_EvalFrameDefault(PyThreadState *tstate, InterpreterFrame *frame, int thr
             if (res == NULL) {
                 goto error;
             }
+            CHECK_EVAL_BREAKER();
             DISPATCH();
         }
 
@@ -4972,6 +4977,7 @@ _PyEval_EvalFrameDefault(PyThreadState *tstate, InterpreterFrame *frame, int thr
             if (res == NULL) {
                 goto error;
             }
+            CHECK_EVAL_BREAKER();
             DISPATCH();
         }