A ME post ME3 is possible if it takes place in an other part of the universe, that way the choice at the end of ME3 hasn't any consequence. But that would mean for Bioware to start from zero, which represents both a lot of work (in an other word budget) and unknowns.
Based on the information we've got, I imagine that we could play in the next ME an other N7 operative, whom mission would be to find prothean artifacts (something similar to Task Force Aurora's mission with the Leviatan) and help to build the Crucible. Then the come back of the Mako to explore worlds would make sense. New ennemies could be mercenaries / groups of technology resellers.
Or as the capn suggested, the action could take place while Shepard is being rebuilded by Cerberus. But then the content of the mission is harder to imagine (kill the last hostile Geth like Shepard at the beginning of ME2, investigate the Reapers' come back ?).





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