Keith,
Sadly, bizarre, unexplainable, irreproducible anomalies are just part of life with Mach3 for many of us. That's why I tossed Mach3 several years ago. I could go days with no problems, then have a day where there was one problem after another. But, since switching to KFlop several years ago, all that is in the past.
For the problem you had, I often found simply re-loading the g-code, and selecting the line to start from usually got me going again, without having to re-start Mach3.
Regards,
Ray L.