Combine 2 tablespoons flour, onion powder, garlic powder, and black pepper in a large plastic bag; place brisket into bag, seal, and shake bag to coat meat with seasoned flour.
Heat vegetable oil in a large heavy pot or Dutch oven over medium-high heat. Brown meat on all sides; reduce heat to low. Whisk onion soup mix in hot water in a bowl until dissolved; pour over the brisket. Pour beer over meat. Add more water as needed to bring level of liquid to halfway up side of the brisket.
Cover and simmer until beef is tender, about 2 hours, adding more water if needed. Remove meat to a platter and cool for 15 minutes. Stir ketchup, applesauce, and Worcestershire sauce into pan juices; whisk 2 tablespoons quick-mixing flour into mixture. Simmer until gravy is thickened, about 5 minutes.
Slice brisket very thinly against the grain and return sliced meat to pot with gravy. Stir to coat meat; simmer 1 more hour.
Transfer meat and gravy to a casserole dish and cover; refrigerate overnight. Skim hardened fat from the meat and gravy before bringing back to a simmer over low heat to serve.
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