The only legitimate purpose of using six.PY3 is for managing a module that runs in both Python 2 or Python 3; for that purpose it's almost essential. When Python 4 eventually comes out you may find vestiges of code that still rely on it, even though it hasn't been required for ages. If PY3 is still True, your code will continue to run just fine without changes. If you find it necessary to manage the upgrade from 3 to 4 I'm sure there will be another package available with the required constants.

Maybe readability? "if six.PY3" is easier on the eyes than "if not six.PY2". At least to me. ;)