I've inverted my mouse's wheel Y axis using xmodmap(1) for my whole X11 session:
  xmodmap -e "pointer = 1 2 3 5 4 7 6 8 9 10 11 12"
(note the "5 4" bit).

This works well everywhere, with scrolling properly inverted (scroll up to push document up in view), apart from GT3K3 applications, which still  works as if the axis wasn't inverted (scroll up to move view towards the top of the document, i.e., move document down).

This happens, for example, with the epiphany-3.6.1-1 and gtk3-3.6.1-1 ArchLinux packages:
1. xmodmap -e "pointer = 1 2 3 5 4 (in a term);
2. test that the Y axis is inverted in a non-GTK3 application;
3. in Epiphany, go to a long document and scroll;
-> Y axis wheel still behaves as if it wasn't inverted.

Other packages (ArchLinux x86_64):
* xorg-server-1.13.0-4
* xorg-xmodmap-1.0.7-1
* xorg-xinput-1.6.0-1
* xf86-input-evdev-2.7.3-2