I use the MP-E 65 handheld with my 1D X, although I haven't tried it with my EOS M. I use it with the MT-24EX twin flash – a strobe is pretty much a requirement for the lens.
If using a 600EX-RT, I'd recommend getting it out and over the subject with a bracket and off-camera cord (or ST-E3-RT). Also, no real need for a softbox on the 600EX. Softness of light comes down to the size of the light source relative to the size of the subject. The bare head of the 600 a few inches from a 1:1 mag subject is like lighting a portrait with a 10-foot softbox.
Having just discovered I can use the bundled 90EX as a master, I can use the 600EX-RT off camera after all! Perhaps still less control than having a fixed bracket, but it's a lot better than I could have hoped. I'll post some results when I can do some macros (when the storms stop spoiling things)