I will discuss two scenarios that give rise to QCD axions with large flavor-violating couplings to fermions at tree-level. The first scenario is a class of generalized DFSZ models with Peccei-Quinn charges compatible with a 2+1 flavor structure, in which the flavor misalignment are treated as free parameters and control both diagonal and flavor-violating axion couplings. This structure allows to construct axion models that have suppressed couplings to nucleons and electrons, thus avoiding the stringent constraints from Supernovae and White Dwarf cooling. The axion can be as heavy as 0.2 eV and therefore be tested at the next generation of helioscopes. In the second scenario the PQ symmetry is identified with a U(1) Froggatt-Nielsen symmetry, so that axion couplings to fermions and photons are directly related to fermion masses and mixings. Both scenarios can be tested by precision flavor experiments like NA62.