Don't see any reason why you can't in mach3 call one head Z and the other A , B or C (or one A the other B) you just don't have some tool offset features but if you zero out each spindle to the tool tip its just numbers. Use linear setup option for the A,B or C axis, not rotary.
It's up to you how you write your programs and setup your machine. The fixture offset still can be used and all you would have to do is edit the second spindle name in a text file. Or use a creative post process.