Preheat the oven to 350°F (175°C). Lightly grease a 9x13-inch baking dish with olive oil or nonstick spray and set aside.
Cook the pasta according to the package directions until al dente. Drain, briefly run under hot water, then toss with 1 tablespoon olive oil in a large bowl and set aside.
In a large saucepan over medium heat, melt 4 tablespoons butter. Whisk in 1/4 cup gluten-free all-purpose flour until combined to form a roux.
Gradually whisk in 5 cups milk, continuing to whisk until smooth. Add salt, garlic powder, onion powder, paprika, mustard powder, and red pepper flakes (if using).
Bring the sauce to a gentle boil over medium heat, then simmer for about 2 minutes while whisking, until slightly thickened.
Reduce the heat to low and, if using, stir in 1/2 cup sour cream until combined. Add 2 cups sharp cheddar, 1 cup white Colby, and 1 cup Parmesan, stirring until the cheeses are fully melted and the sauce is smooth.
Toss the cheese sauce with the cooked pasta until evenly coated. Transfer the mixture to the prepared baking dish and spread into an even layer.
In a medium bowl, combine 1 1/2 cups gluten-free cracker crumbs with 6 tablespoons melted butter and stir with a fork until evenly moistened.
Evenly sprinkle the remaining topping cheeses—1 cup white Colby, 1 cup cheddar, and 1/2 cup Parmesan—over the pasta, then sprinkle the buttery cracker crumbs on top.
Bake uncovered in the preheated oven for 25–30 minutes, until the top is golden brown and the casserole is bubbly.
Remove from the oven and let rest for 10–15 minutes before serving.