"Flex Fuel" isn't an issue (I assume you mean E85 and similar) if you use injector duty cycle as the basis of your calculations. Total injector "on" time gives you fuel consumption, regardless of the AFR, or even if it was a stoichiometric burn.
If you are trying to find live efficiency data, this becomes more complex.
But simple fuel consumption is only a matter of injector(s) rate (cc/min, lb/hr, etc) and how long the injector stays open. Fuel injected can be assumed "consumed" even if not fully burned.
I do agree, that if you need to know exact number of moles of oxygen for your "flex" hydrocarbon juice, this will be nearly impossible. E85, for instance, is a variable blend of corn liquor moonshine (errrr, I meant ETOH or ethyl alcohol) and various x-tanes of "gasoline" hydrocarbons, along with some hygroscopically absorbed water. Problem is, goverment controls on E85 are not all that tight, nor is there much enforcement. I'm big into extreme turbocharging, and E85 is a great way to combat intake heat. But some E85 may be as low as 70% moonshi... ETOH. Bottom line, you need to know the number of carbon atoms in every style of hydrocarbon to determine ultimate stociometric burn, but even this is hotly debated as "stochio" burn does NOT mean the highest power or fuel efficeiency. But I'm rambling, and I don't think this is what you asked...
Also note that E85 ETOH blend (and "top-fuel" methanol) has a lower BTU content than pure "gasoline", for identical quantities. The value is in the higher compression and BMEP that can be achieved.
Still, consumption is # injectors X injector rate X IDC ("on time")