Because mIRC strings are unquoted it's impossible for mIRC to know whether that's a single string with commas in or whether you tried to give 3 parameters to the identifier. As mths said, simply assign the string to a variable first:
var %tempvar = One, Two, Three
say $lower(%tempvar)

It's better that mIRC behaves in a consistent and future-proof manner like this, instead of making exceptions to when and where commas separate parameters and where they're just part of a string.

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