As this thread, and the fact that it's relatively recent came up when I experienced something similar, I thought I'd share some notes.
I had a corrupted USB drive being used for unRAID, which I replaced and re-keyed successfully. When I was generating this new key, I thought "why not?" and ENABLED it to boot in UEFI mode. Now, I've set my BIOS for Legacy (Gigabyte x570 AORUS MASTER), so I didn't ASSUME this would create any issues.
After initial reboot - and fixing failed NVIDIA plugins (which I didn't need, as I'm not doing Docker passthrough), the following error kept occurring:
qemu-system-x86_64: vfio_region_write(0000:0c:00.0:region3+0x15004, 0xabcdabcd,4) failed: Device or resource busy
I re-bound VFIO, ran all the listed commands, and still had no luck.
While ruling out other issues, I checked the BIOS, and even though "Legacy ONLY" was enabled, it was listing UEFI for the unRAID USB key.
I selected the alternative option for the drive, restarted, and the VM fired up without issue.
Hope this "accidental UEFI selection" helps someone else.
Cheers, -Ian