Bring a large pot of lightly salted water to a boil. Add pasta and cook for 8 to 10 minutes or until al dente; drain.
In a large saucepan over medium heat, melt 2 tablespoons butter. Whisk in flour and cook, stirring, 1 minute. A little at a time, whisk in milk, mustard, salt, pepper and hot sauce. Bring to a gentle boil, stirring constantly. Boil 1 minute, then remove from heat and whisk in pepperjack, Cheddar and Parmesan until smooth. Stir in cooked pasta and pour into shallow 2 quart baking dish.
Melt remaining 2 tablespoons butter. Stir in bread crumbs and chili powder. Sprinkle over macaroni mixture.
Bake in preheated oven 30 minutes. Let stand 10 minutes before serving.