This shows up on my screen when I have a lot of tabs or programs open, but sometimes it shows up without warning.
Hmm. What model MBP do you have? There have sometimes been display issues with newly-released Apple products that have required firmware to fix. It could also be something faulty in the hardware. Is the machine still covered under AppleCare? I might just bring it to a Genius bar.
I forgot the major part. When the box shows up, the screen doesn't respond to either mouse. I try esc, I try command + option + esc, I try F3, but nothing works. I have to restart it.