Found some interesting behavior debugging this issue: https://review.opendev.org/c/openstack/horizon/+/797076
tox -r -epep8 generates broken env with version discrepancy:
$ pip check
flake8 3.7.9 has requirement pycodestyle<2.6.0,>=2.5.0, but you have pycodestyle 2.7.0.

Ubuntu Focal, Python 3.8, tox 3.13.2, pip 20.0.2