2000 Chevy Silverado severe misfire

Is the only code you are getting a random misfire? Have you checked or replaced the crank sensor? Control module?

If it is a 4.3, it is in the lower portion of the timing cover. If it is 4.8, 5.3, or 6.0 it is on the right rear of the engine block, above the starter.
Has the misfires ever been graphed to determine which cylinder(s). It could be possible that you have a degrading cat causing a whole bank of cylinders to misfire. When there is no airflow, the particles of monolith settle in the bottom. As exhaust passes through, it picks up the particles and starts resticting exhaust flow. This restriction will result in misfires, as no air can be drawn in for adequate combustion.