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Low-resolution spectroscopy is a frequently used technique. Aperture prism spectroscopy in particular is an important tool for large-scale survey observations. The ongoing ESA space mission Gaia is the currently most relevant example. In this work we analyse the fundamental limitations of the calibration of low-resolution spectrophotometric observations and introduce a calibration method that avoids simplifying assumptions on the smearing effects of the line spread functions. To this aim, we developed a functional analytic mathematical formulation of the problem of spectrophotometric calibration. In this formulation, the calibration process can be described as a linear mapping between two suitably constructed Hilbert spaces, independently of the resolution of the spectrophotometric instrument. The presented calibration method can provide a formally unusual but precise calibration of low-resolution spectrophotometry with non-negligible widths of line spread functions. We used the Gaia spectrophotometric instruments to demonstrate that the calibration method of this work can potentially provide a significantly better calibration than methods neglecting the smearing effects of the line spread functions.