Hmm, I mostly use Calibre for epub reading, and was not aware of it writes bookmark back to epub itself. Do you mean some e-ink reader updates .epub whenever you add bookmark? That seems an odd implementation.
I'm not sure what gets modified, but I've stopped using the Calibre epub-reader because I found that everytime I've read a book, my rsync backup script found changes in the epub. I once checked in the epub (it's a zipfile after all) and there seems to be an extra file added. Removing that solves the issue. It was a long time ago, I can't remember details.
Now I just copy my epub's to a temporary file before reading.
FWIW, there is a setting to make Calibre's reader to save its bookmarks file outside the epub. I think the setting needed to be set in the reader itself.
Now I just copy my epub's to a temporary file before reading.