Whisk together sugar, egg yolks, and vanilla in a medium bowl until mixture is pale yellow and reaches the ribbon stage, meaning that when you lift the whisk, the mixture is aerated enough that it falls into the bowl in thick trails, about 3 to 4 minutes. Add flour; whisk until smooth.

Bring milk to a boil in a medium saucepan over medium, about 3 minutes. Gradually add milk to egg yolk mixture, whisking constantly. Return mixture to saucepan. Bring to a boil over medium, whisking constantly, about 3 minutes. Boil mixture, whisking constantly, 1 minute. Transfer mixture to a medium bowl; press plastic wrap directly onto surface. Let cool to room temperature, about 1 hour. Mixture can be chilled, covered, for up to 3 days.

Preheat oven to 375°F with oven rack in lower third of oven. Stir together granulated sugar and flour in a small bowl; set aside. Cut a 24- x 12-inch piece of parchment paper; fold lengthwise 3 times (letter-style). Wrap paper around outside top of a 1-quart soufflé dish to form a collar extending 2 inches above rim; secure tightly with string. Rub inside of soufflé dish and parchment collar with butter. Dust with sugar mixture, shaking out excess. Chill dish at least 15 minutes.

Stir together crème pâtissière, Grand Marnier, and orange zest in a large bowl. Beat egg whites in bowl of a heavy-duty stand mixer on medium speed until glossy and stiff peaks form, about 4 minutes. Whisk about one-third of egg whites into crème pâtissière mixture until well incorporated. Gently fold in remaining egg whites until just incorporated. Pour mixture into prepared dish. Place dish on a rimmed baking sheet, and bake in preheated oven until soufflé is puffed and golden brown, 40 to 45 minutes. Sprinkle with powdered sugar. Serve immediately.