I have a 2001 Honda accord 3.0L v6 that is misfiring on multiple cylinders. If I pinch off the fuel return line it runs fine again? So I replaced the fuel regulator and it did nothing back to misfiring again. Pinch off the return line and runs fine?

Check for a vacuum leak, especially around the upper intake manifold (UIM). Also, only use the original NGK spark plugs that came in the car, gapped to spec.