flame-cube I don't see why you can't. Tilemap should do this just fine. You can assign different size collision maps to different size sprites, not hard at all. Consult the docs for more. Just remember to know what your max tile size is, as ultimately any tile art has to be, well, within a tile. However, Godot also allows custom polygon drawing here so you should be able to do whatever you need. Just figure out a max square size, make sure all your tiles can fit in that size, and bam, you're done.
Alternative: You could also just build your larger objects out of individual tiles and build bigger physics parts piece by piece. Not glamorous I know, but effective and a bit simpler.
Either way, yes. You can totally do this.