I haven’t seen anyone else suggest this and it fixed my problem.
I have a bad habit of ignoring Windows updates for months or even years at a time (I disable auto-updates). After trying everything there is to try (update video drivers, update BIOS, run as administrator, set process priority to High, tweak the .INI file, verify/reinstall game, etc.) I finally decided to try updating Windows. Specifically after I installed the latest .NET framework update my crashes have stopped completely, but I still updated the rest just to make sure.
Once I could actually get into the game, I set the graphics to Medium, enabled VSYNC, and actually ENABLED DX12. It bumped my claptrap-dance load screen to about a minute, but it completely smoothed out the framerate for me both in Windowed and Fullscreen. My guess is that out of date Windows features and security updates might be conflicting with Denuvo or the game’s framework or something, and might be why DX12 is so buggy. I just finished a 10-hour session with no real performance issues, totally playable now.
If you’ve tried everything else and nothing has worked, try updating Windows and see if that helps!