Why couldn't you use a Chromebook comfortably because you are left handed? I am left handed and I use a mouse just like any other right handed person. I don't know anyone who is left handed and uses the mouse with their left hand. So saying that 20% of the population can't use Chromebooks comfortably isn't right in my opinion. I'm sure for some people it is a problem, I'm not trying to say that it's not. I also think that it's pretty stupid that you can't reassign the mouse buttons and I really don't like their response to the problem. Or is there a different reason why it should be uncomfortable?

I though Chrome has a setting to swap the primary mouse button?

Chrome OS, Settings, Mouse, Swap primary button (or something like that, I'm using the German locale).

Since they already have this setting, one wonders why it is not trivial to extend it to allow remapping of all the available buttons.

The left and right button (plus scroll wheel these days) are standardized and pretty much guaranteed to work on arbitrary USB mice because otherwise users would revolt. Even reliable support for the middle button was a matter of luck for a long time, years ago (that was before scroll wheels were a thing).

Everything else the OS can't really expect to work. There's a reason why vendors of such advanced input devices provide their own config tools for Windows and macOS: both systems don't even try to support that clusterfuck out of the box.

After looking at the USB HID protocol for mice, I see what you mean. I was making the assumption that the button was detected by the OS and just not mappable by the user, but the protocol doesn't specify past the first 3 buttons so that isn't necessarily true.