What model year is your E350? Is it the extended body with raised roof?
I ask as I have an '05 E350 with raised roof, formerly a wheel chair lift equipped Club Wagon---that was the first year of the "fly by wire" throttle system replaced the cable opening from years previous (1997>2004).
I'd characterize its performance as "sluggish" especially from a dead stop. When at freeway speeds in top gear its responsive enough for a big vehicle.
Certainly not doubting the cat could be an issue but could just be the nature of the vehicle too---that's a lot of sheet metal and fiberglass to move down the road.